the natural history of dilated cardiomyopathy (dcm) thomas zegkos cardiomyopathies lab ahepa...

THE NATURAL HISTORY OF DILATED CARDIOMYOPATHY (DCM)Thomas Zegkos

Cardiomyopathies Lab

AHEPA University Hospital

DEFINITION OF DILATED CARDIOMYOPATHY

“The presence of left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension, valve disease) or coronary artery disease sufficient to cause global systolic impairment”.

Elliot P et al. EHJ 2008

CAUSES OF DCM

CAUSES OF DCM IN PATIENTS WITH INITIALLY UNEXPLAINED CARDIOMYOPATHY

Felker et al NEJM 2000

Disorder05

101520253035404550

IDCM

Myocarditis

Ischmic CM

Infiltrative disease

Peripartum CM

Hypertension

HIV

CTD

Substance abuse

EPIDEMIOLOGY OF IDCM

ANNUAL INCIDENCE 5-8/100,000

PREVALENCE 36/ 100,000

INCREASED RISK ASSOCIATED WITH: MALE GENDER BLACK RACE CHRONIC BETA-AGONIST USE

Dec GW, Fuster V. NEJM 1994;331:1564-75

FAMILIAR DCM

Over 20-50% of patients with IDCM Over 30 genes responsible have been discovered

GENESLamin A/Cδ-sarcoglycanDystrophinDesminVinculinTitinTroponin-Tα-tropomyosinß-myosin heavy chainActinMitochondrial DNA mutations

Fatkin D, et al. NEJM 1999;341

LAMINOPATHIES

6% of all DCM patients 7.5% of familiar forms 33% of DCM patients with conduction disturbances

Parks S, et al, Am Heart J 2008

CLINICAL PRESENTATION OF DCM

Heart failure symptoms 75%-85%

Chest angina 8%-20%

Emboli (systemic or pulmonary) 1%-4%

Syncope <1%

Sudden cardiac death <1%

Dec GW, Fuster V. NEJM 1994;331:1564-75

DCM EVALUATION

Detailed family history and screening of first degree relatives if necessary Complete blood count Metabolic panel Thyroid function tests Cardiac biomarkers B-type natriuretic peptide assay Chest radiography Echocardiography Cardiac magnetic resonance imaging (MRI) Electrocardiography (ECG) Endomyocardial biopsy may be useful in case of:

Recent onset of rapidly deteriorating cardiac function Patients receiving chemotherapy with doxorubicin Patients with systemic diseases with possible cardiac involvement (eg,

hemochromatosis, sarcoidosis, amyloidosis, Löffler endocarditis, endomyocardial fibroelastosis)

NATURAL HISTORY OF DCM

HEART FAILURE AND FUNCTIONAL STATUS

SUR

VIV

AL

Asymptomatic

100%

0Mild Moderate Severe

ANNUAL MORTALITY

< 5% 10% 20 - 30 % 30 - 80%

CAUSE OF DEATHΥ

SUDDEN DEATH 40%CONGESTIVE HEART FAILURE 40%

OTHER CAUSES 20%

Acute event

V McMurray JJ, et al. Lancet 2005

CAUSES OF DEATH BASED ON NYHA CLASS

MERIT-HF study group. LANCET 1999

DIFFERENCES IN NATURAL HISTORY OF DCM ETIOLOGIES

Felker et al NEJM 2000

SURVIVAL IN IDCM VERSUS MYOCARDITIS

0

20

40

60

80

100

0 2 4 6Years

Surv

ival

(%

)

Myocarditis (n=27)IDCM (n=58)

Grogan, et al JACC 1995

SURVIVAL IN IDCM VERSUS ALCOHOLIC DCM

Merello G, et al JACC: HEART FAILURE 2015

SURVIVAL IN IDCM VERSUS SARCOIDOSIS CARDIOMYOPATHY

Yazaki Y, et al. Am J Cardiol 1998

NATURAL HISTORY OF LAMINOPATHIES

Age related penetrance with early onset atrial arrhythmias followed by conduction disease, often with mild LV dilatation and systolic dysfunction.

Over 60% of patients experience cardiovascular death or major cardiovascular events by the age of 45

46% of mortality of carriers due to sudden death

Taylor G, et al. JACC 2003Van Berlo J, et al. J Mol Med 2005

PROGNOSTIC FACTORS OF DCM

ECHOCARDIOGRAPHIC FINDINGS Degree of impairment in LVEF Extent of left ventricular enlargement Diastolic dysfunction Coexistent right ventricular dysfunction

CLINICAL FINDINGS Favorable prognosis: NYHA < IV, younger age,

female sex Poor prognosis: Syncope, persistent S3 gallop, right-

sided heart failure, atrial fibrillation, AV or bundle branch block, hyponatremia, troponin elevation, increased BNP, maximum oxygen uptake < 12 mg/kg/min

AHA/ACC 2013 AND ESC 2015 INDICATIONS FOR ICD IMPLANTATION IN DCM

Predictors of SCD used in the guidelines also predict overall mortality and simply reflect severity of disease.

45 studies. 6088 DCM patients enrolled

Goldberger J, et al. JACC 2014

SYNCOPE IN DCM

Syncopal events imply a higher risk of SCD regardless of the proven etiology of the syncope.

These patients with ICD implantation receive similar clinical benefits to secondary prevention cases.

Knight B, et al. JACC 1999

LATE GADOLINIUM ENHANCEMENT

Gulati A, et al. JAMA 2013

LAMINOPATHIES RISK FACTORS FOR MAJOR EVENTS IN 269

PATIENTS Baseline LVEF < 45% Non-sustained ventricular tachycardia Male gender

van Rijsingen IA, et al. JACC 2012

373 patients with an evaluation consistent with IDCM or myocarditis

Fewer than 6 months of symptom duration

McNamara D et al. JACC 2011

LVEF IMPROVEMENT IN IDCM AFTER OMT (IMAC2 STUDY)

Solid bars: lvedd <6,00 cm

Shaded bars: lvedd 6,00 to 7,00 cm

Open bars: lvedd >7,00 cm

McNamara D et al. JACC 2011

• 70% demonstrated an increase of 10 ejection fraction units,• 39% demonstrated an increase of 20 U or more.• In 25% the LVEF had normalized (0.50 or more).

LVEF IMPROVEMENT IN ALCOHOLIC DCM

Merello G, et al JACC: HEART FAILURE 2015

LVEF IMPROVEMENT IN CHEMOTHERAPY INDUCED DCM

Cardinale D, et al JACC 2010

LVEF IMPROVEMENT IN CARDIAC SARCOIDOSIS

Chou CZ, et al. Am J Cardiol 2004

ROLE OF LVEF IMPROVEMENT ON THE NATURAL HISTORY OF DCM

Steimle AE, et al. JACC 1994;23:553-9

SURVIVAL IN IDCM (1975-2000)

25-30% annual mortality 50% five-year mortality

Dec GW, Fuster V. NEJM 1994;331:1564-75

SURVIVAL IN IMAC2 (2011)

94% transplant free survival at 1st year

88% at 4 years

McNamara D et al. JACC 2011

603 patients with IDCM 4 enrollment periods:

Castelli G, et al. Circ Heart Fail. 2013

1977-1984: pre ACEI

1985-1990: ACEI introduction

1991-2000: B-blockers introduction

2001-2011: Devices introduction

CHANGES IN MANAGEMENT OF DCM

Castelli G, et al. Circ Heart Fail. 2013

CHANGES IN MANAGEMENT OF DCM

Castelli G, et al. Circ Heart Fail. 2013

CARDIOVASCULAR AND HEART FAILURE MORTALITY REDUCTION

HF mortality decreased: 53% for period 2 74% for period 3 90% for period 4compared to period 1

5 year event-free rate: 62% for period 1 74% for period 2 84% for period 3 93% for period 4

Castelli G, et al. Circ Heart Fail. 2013

SUDDEN DEATH RATE REDUCTION

87% risk reduction in period 2000-2010 compared to period 1977-1984

Castelli G, et al. Circ Heart Fail. 2013

AHEPA CARDIOMYOPATHIES CENTER COHORT

183 DCM patients

Idiopathic Familiar Myocarditis Alcoholic Chemotherapy Other0

5

10

15

20

25

30

35

40 37.7

24

10.4 9.8

0.5

17.6

%

AHEPA CARDIOMYOPATHIES CENTER COHORT

183 DCM patients

CEI/ARB B-Blocker Diuretics MRA0

10

20

30

40

50

60

70

80

77.6 75.4

64.5

44.3

%

AHEPA CARDIOMYOPATHIES CENTER COHORT

After a mean follow up of 6±4 years, 9,8% died NYHA class and LVEF were independent predictors

P=0,02 P=0,009

AHEPA CARDIOMYOPATHIES CENTER COHORT

1,6% suffered SCD 18% of the patients received ICD

Primary prevention Secondary prevention0

10

20

30

40

50

60

70

80

78.8

21.2

ICD %

AHEPA CARDIOMYOPATHIES CENTER COHORT

21% of ICD patients received appropriate interventions

Primary Prevention Secondary prevention0

10

20

30

40

50

60

11.5

57.1

Appropriate interventions %

CONCLUSIONS

DCM is an heterogeneous disease with variable natural history.

The natural history of DCM has changed substantially over the last decades.

The prognostic factors of DCM, especially for SCD, still remain a subject of controversy.

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